Serological studies indicate that more than 80% of the world's adult population is infected with JC virus, a papovavirus. The mode of transmission of this virus is unknown and acute infection has not been recognized as a cause of an identifiable illness. However, JCV is the cause of progressive multi focal leukoencephalopathy (PML), a formerly rare demyelinating disease of the brain. PML has become common in the face of the HIV pandemic affecting approximately 5% of all AIDS patients, usually during advanced stages of immunosuppression. JCV remains latent in the reticuloendothelial system following the initial infection. Demonstration of the virus in tonsillar tissue suggests an oropharyngeal or respiratory mode of transmission. JCV is also expressed periodically in peripheral blood lymphocytes (PBLs). These cells share regulatory regions for the virus with CNS glial cells infected in PML. While JCV can be identified in the PBLs of approximately 5% of otherwise normal individuals, it is demonstrable in the PBLs of approximately 50% of immunosuppressed individuals, including those with AIDS, and in 90% of persons with AIDS-associated PML. The expression of JCV in the oropharyngeal fluids has not been previously determined. We hypothesize that JCV is shed in oropharyngeal fluids and that its presence in these fluids will correlate with both its presence in PBLs and the severity of immunosuppression. The aims of this study include identifying JCV in saliva and throat washings in three populations (normal controls, HIV-infected persons, and persons with AIDS-associated PML); determining whether a correlation exists between JCV presence in oropharyngeal fluids and in PBLs; and determining whether JCV shedding from the oropharynx correlates with the degree of immunosuppression. This line of investigation would add credence to an oropharyngeal mechanism of JCV transmission and may ultimately lead to the clinical identification of an acute illness attributable to this pathogen.